The pulmonary toxicity of oxygen is one of the limiting factors in the physician's capability of treating acute respiratory insufficiency. Currently, little is known about oxygen toxicity and nothing useful about its control. Clinical impression suggests that patients in respiratory failure, having large Qs/QT, are sometimes much more resistant to oxygen poisoning than would be expected from data derived from normal human volunteers. The hypothesis that a high A-aDO2 created by surgical shunt provides partial protection against pulmonary O2 damage has been substantiated at hyperbaric pressures, but apparently does not obtain in the normobaric clinical setting. In current studies, pulmonary damage analagous to that seen in some kinds of respiratory failure has been produced by administration of oleic acid to rabbits. This insult produces sublethal hemorrhagic pulmonary edema. Injected, lung damaged animals exposed to 100% O2 at atmospheric pressure in a controlled environment survive significantly longer (p less than 0.01) than normal controls before succumbing to O2 toxicity. This suggests, at least in this experimental model, that the toxic effects of oxygen and of prior lung pathology are not additive but, to some extent, antagonistic. This is in accord with clinical impressions of relative oxygen tolerance in patients in respiratory failure. Prior experiments indicate that the low or normal systemic oxygen levels in the experimental group are probably not etiologic in the protection seen. Current research is directed at an elucidation of the mechanism of this apparent protection.